UNLABELLED Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases. Evidence from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio, is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia. Combination regimens of piperacillin/tazobactam plus an aminoglycoside are used to treat patients with severe nosocomial (hospital-acquired) infections. In clinical trials, piperacillin/tazobactam was significantly more effective than ticarcillin/clavulanic acid in terms of clinical and microbiological outcome in patients with community-acquired pneumonia. In patients with intra-abdominal infections, clinical and bacteriological response rates were significantly higher with piperacillin/tazobactam than with imipenem/cilastatin (administered at a dosage lower than is recommended in countries outside Scandinavia). Piperacillin/tazobactam in combination with amikacin was at least as effective as ceftazidime plus amikacin in the treatment of ventilator-associated pneumonia and was significantly more effective than ceftazidime plus amikacin in the empirical treatment of febrile episodes in patients with neutropenia or granulocytopenia. In other trials, the efficacy of piperacillin/tazobactam was similar to that of standard aminoglycoside-containing and other treatment regimens in patients with intra-abdominal, skin/soft tissue or gynaecological infections. Piperacillin/tazobactam is generally well tolerated. The most frequent adverse events are gastrointestinal symptoms (most commonly diarrhoea) and skin reactions. The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given in combination with an aminoglycoside than when given as monotherapy. CONCLUSION Because of the broad spectrum of antibacterial activity provided by piperacillin/tazobactam, it is useful for the treatment of patients with polymicrobial infections caused by aerobic or anaerobic beta-lactamase-producing bacteria. Piperacillin/tazobactam appears to have a particularly useful role in the treatment of patients with intra-abdominal infections and, in combination with amikacin, in the treatment of patients with febrile neutropenia, especially given the current prevalence of Gram-positive infections in this group.

/pdf/piperacillin-tazobactam-an-updated-review-of-its-use-in-the-2fstttylp0.pdf

Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections.

The mechanisms of resistance to -lactam antibiotics in 325 isolates of Pseudomonas aeruginosa were examined. These isolates were selected because of their resistance to meropenem and imipenem (breakpoint, >4 mg/L), carbenicillin (>128 mg/L), ceftazidime (>8 mg/L), piperacillin and ticarcillin/clavulanate (>64 mg/L). The most frequent mechanism of resistance was -lactamase-independent, so called ‘intrinsic resistance’, which was found in 183 isolates and was probably due to impermeabilit y and/or efflux mechanisms. -Lactamase-mediated resistance was demonstrated in 111 strains (11.1%). Derepression of Ambler Class C chromosomal -lactamase was detected in 64 isolates, most of which were resistant to ceftazidime and piperacillin but susceptible to meropenem, whereas secondary plasmid-encoded -lactamases were found in 34 isolates, all of them resistant to carboxypenicillins and ureidopenicillins and susceptible to carbapenems. Twelve strains showed more than one plasmidencoded -lactamase plus derepression of chromosomal Class C enzyme. Resistance to carbapenems was independent of resistance to other -lactam antibiotics, indicating a different mechanism of resistance, probably due to the loss of the D2 porin. In total, 32 strains were resistant to carbapenems: 24 only to imipenem and eight to both imipenem and meropenem.

Mechanisms of beta-lactam resistance amongst Pseudomonas aeruginosa isolated in an Italian survey.

The in vitro activity of levofloxacin and eight other antimicrobial agents against 60 clinical isolates of Stenotrophomonas maltophilia was determined by an agar dilution method using 10 4 and 10 6 cfu/spot inocula. At the lower Inoculum, 85.0% of the isolates were susceptible to levofloxacin but only 58.3% were susceptible to ofloxacin; at the higher inoculum, 78.3% were susceptible to levofloxacin and 36.7% to ofloxacin. In time-kill studies, levofloxacin exerted bactericidal activity within 4 h. With ofloxacin and ciprofloxacin bacterial regrowth was observed after 8 h. Levofloxacin may represent an alternative drug in the treatment of infections caused by S. maltophilia.

Levofloxacin in vitro activity and time–kill evaluation of Stenotrophomonas maltophilia clinical isolates

UNLABELLED Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. CONCLUSIONS Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

The in vitro activity of levofloxacin against 300 Pseudomonas aeruginosa isolated from hospitalized patients, with the exception of those recovered in intensive care or hematology units, was compared to ofloxacin, ciprofloxacin, piperacillin, amikacin, ceftazidime and imipenem. Imipenem showed the best activity (81.6%), followed by piperacillin (80.7%). The activity of levofloxacin was equal to that of ciprofloxacin (75.3%) but was more active than ofloxacin (58.1%). Moreover, the MIC values of levofloxacin did not show any statistical difference using two different inocula. Levofloxacin shows an excellent bactericidal activity being generally within one doubling dilution of the MIC. These results were also confirmed by the time-killing studies. In conclusion, according to the in vitro activity, levofloxacin could be considered a good option for the treatment of infections sustained by Pseudomonas aeruginosa, and clinical experiments are required to corroborate our in vitro data.

Is levofloxacin as active as ciprofloxacin against Pseudomonas aeruginosa

From September 1994 to March 1995 an Italian multicenter in vitro study to evaluate the susceptibility of piperacillin/tazobactam compared with that of imipenem, ceftazidime, ceftazidime, ceftriaxone, cefotaxime and ampicillin/sulbactam against aerobic bacterial pathogens isolated in 132 different hospitals, was undertaken. In total, 26,732 isolates were collected but only 25,266 aerobic bacteria were able to be evaluated (16,863 Gram-negative and 8,403 Gram-positive). Escherichia coli was the most frequent pathogen isolated (25.9%) followed by Staphylococcus aureus (14.9%), Pseudomonas aeruginosa (13.9%), Enterococcus faecalis (8.2%) and Klebsiella pneumoniae (5.9%). Piperacillin/tazobactam had a general spectrum of activity (84.8% susceptible strains) comparable to imipenem (87.9%), and was distinctly greater than ceftazidime (71.1%).

Susceptibility survey of piperacillin/tazobactam and some beta-lactam comparators in Italy.

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Susceptibility survey of piperacillin/tazobactam and some beta-lactam comparators in Italy.